Complete remission and long-term survival in a child with relapsed medulloblastoma with extensive osteosclerotic bony metastasis with a novel metronomic chemobiological approach.

Extraneural metastases in medulloblastoma are rare. We report a boy with medulloblastoma who was initially treated with gross total excision of primary tumor followed by radiotherapy. Six years later, he developed disseminated osteosclerotic bony relapse associated with bone marrow involvement. He was successfully salvaged with metronomic low-dose cyclophosphamide, etoposide, and zoledronic acid. In patients with medulloblastoma and bone pain, metastases to bone should be excluded, and medulloblastoma should be considered while investigating osteosclerotic bone lesions. Furthermore, metronomic chemotherapy should be considered in this setting until better therapeutic modalities emerge.

Calvarial metastasis of a renal cell carcinoma, mimicking a primary alveolar soft part sarcoma, in a young girl-a rare case report.

Renal cell carcinoma (RCC) is characterized by an unpredictable clinical behavior. It has a tendency for early metastasis, which, at times is the initial presentation and therein poses a diagnostic challenge. We present a rare case of a disseminated RCC in a 15-year-old girl, who primarily presented with an occipital soft tissue mass. Computed tomography (CT) of the head revealed a soft tissue mass in the scalp, eroding the occipital bone and extending intracranially. Biopsy examination showed overlapping features of an alveolar soft part sarcoma (ASPS) and a RCC. Immunohistochemistry (IHC) showed diffuse positivity for CD10 and focal positivity for vimentin. Cytokeratin (CK) and epithelial membrane antigen (EMA) were negative. The patient was recommended a clinical 'work-up' to rule out a possible primary in the kidneys. Her CT scan abdomen unraveled a large, lobulated, heterogeneous cystic mass, involving the middle and upper pole of the left kidney. Diagnosis of a metastatic RCC was ascertained. The present case represents a rare manifestation of a RCC metastasizing at an unusual location i.e. calvarium in the youngest patient known, so far and masquerading a primary ASPS. It also highlights the value of clinico-patho-radiological correlation, including CD10 as a useful IHC marker in diagnosing a RCC in young patients, especially when histopathological features overlap with ASPS.

Disseminated cysticercosis: role of whole body Magnetic Resonance Imaging.

UNLABELLED: Cysticercercosis is a parasitic infection that is commonly seen in developing countries. Treatment of cysticercosis can precipitate an intense inflammatory response which may further worsen the symptoms. Whole body MRI is an upcoming tool for screening of diseases. It can be acquired in the same setting as a brain MRI in reasonable time without any additional hardware. We present a case wherein whole body MRI was used to evaluate disseminated cysticercosis. It can prove as useful screening tool to gauge the disease load and modify the treatment plan accordingly, especially in endemic areas. KEY WORDS: disseminated cysticercosis, whole body MRI.

Internal target volume for post-hysterectomy vaginal recurrences of cervical cancers during image-guided radiotherapy.

OBJECTIVE: The outcome of post-surgical recurrences of cervical cancer may be improved through radiation dose escalation, which hinges on accurate identification and treatment of the target. The present study quantifies target motion during course of image-guided radiotherapy (IGRT) for vault cancers. METHODS: All patients underwent planning CT simulation after bladder-filling protocol. A daily pre-treatment megavoltage CT was performed. All translations and rotations were recorded. Post-registration displacement of gross tumour volume (GTV) and centre of mass (COM) of GTV was independently recorded by two observers for fractions one to seven. Day 1 image sets served as reference images against which the displacements of COM were measured. We calculated the displacements of common volume (CV) and encompassing volume (EV) of GTV for both the observers. RESULTS: A total of 90 image data sets of 15 patients were available for evaluation. Individual patient GTV and average GTV by both the observers were comparable. The average shifts for EV were 2.4 mm [standard deviation (SD) ±1.2] in the mediolateral, 4.2 mm (SD ±2.8) in the anteroposterior and 4.0 mm (SD ±2.1) in superoinferior directions. Similarly, the average shifts for CV were 1.9 mm (SD ±0.6) in the mediolateral, 3.7 mm (SD ±2.7) in the anteroposterior and 4.4 mm (SD ±2.7) in superoinferior directions. Using Stroom's/van Herk's formula, the minimum recommended margins would be 4.5/5.2, 8.2/9.4 and 7.3/8.3 mm, respectively, for lateral, anteroposterior and superoinferior directions. CONCLUSION: Differential directional internal margin is recommended in patients undergoing IGRT for post-surgical recurrence of cervical cancers. ADVANCES IN KNOWLEDGE: Internal organ motion of vault cancers can be accounted for by a directional margin to the gross tumour.

Successful management of multi-focal hepatic infantile hemangioendothelioma using TACE/surgery followed by maintenance metronomic therapy.

Infantile hepatic hemangioendothelioma (IHE) is a rare angiogenic tumour with diverse clinical presentations and varied course ranging from spontaneous regression to life-threatening complications. The authors report a 2-year boy who presented with respiratory distress and was identified as a case of inoperable multi-focal hepatic IHE. He showed a transient response to trans-arterial-chemo-embolisation and liver resection but had progressive disease despite chemotherapy (prednisolone/vicristine/ifosfamide/cisplatin). Thereafter, he was successfully managed with metronomic therapy using cyclophosphamide and tamoxifen.

Evaluation of diffusion-weighted imaging as a predictive marker for tumor response in patients undergoing chemoradiation for postoperative recurrences of cervical cancer.

PURPOSE: To investigate diffusion-weighted imaging (DWI) as a response biomarker in patients undergoing chemoradiation for postoperative recurrences of cervical cancer. MATERIALS AND METHODS: From October 2008 to March 2011, 20 patients were included. All underwent T2-weighted (T2W) and DWI before and after chemoradiation. Gross tumor volume (GTV), lateral extent, apparent diffusion coefficient (ADC), and presence of regions of focally restricted diffusion were determined at baseline. Response to chemoradiation was categorized as either partial or complete. Receiver operator characteristics (ROC) curve identified thresholds of GTV and ADC that best predict for partial response. Univariate and multivariate analysis were performed on SPSS version 15. RESULTS: The median GTV was 24.5 cc (4.1-110 cc). Central and lateral disease was present in 8 and 12 patients, respectively. The median ADC was 1 × 10 -3 mm² /s (0.8-1.3 × 10⁻³ mm² /s) and 12/20 (60%) patients had focal restricted diffusion. Overall 10/20 patients had partial response. ROC analysis identified volume of 25 cc or higher [sensitivity = 80%, specificity = 80%, area under curve (AUC) = 0.76, P = 0.04] and ADC more than 1 × 10⁻³ mm² /s (sensitivity = 70%, specificity = 50%, AUC = 0.62; P = 0.34) to best predict for partial response. On univariate analysis bulky disease (77.7% vs. 27%; P = 0.03), lateral disease (66.6% vs. 25%; P = 0.08), and focal regions of restricted diffusion (66.6% vs. 25%; P = 0.06) predicted for partial response to chemoradiation. All factors continued to be significant on multivariate analysis. On restricting analysis to bulky tumors ADC greater than 0.95 × 10⁻³ mm² /s predicted partial response with high sensitivity (85.7%) and specificity (100%) (AUC 0.96; P = 0.05). On univariate analysis lateral disease (P = 0.04), high baseline ADC (P = 0.07) predicted for partial response. CONCLUSIONS: Baseline ADC and focal regions of ADC restriction predict for partial response with moderate sensitivity and specificity in patients with postoperative recurrences of cervical cancer and need to be validated in larger cohort.

Quantitative estimation of doses to salivary glands from using brachytherapy in head and neck cancers.

PURPOSE: To quantify the percentage doses received by salivary glands (SGDs) in head and neck interstitial brachytherapy (BT). METHODS AND MATERIALS: The study included 43 patients who underwent high-dose rate iridium-192 implant for oral cavity and oropharyngeal lesions treated with BT as a boost. BT dose varied with disease stage and external radiation dose, with the total mean dose of 66±4Gy. Patients were divided into two groups, midline and lateralized, based on anatomic implant location. Different dose parameters such as D(max), D(mean), DV(30%) of individual glands were derived from dose volume histogram representing the percentage maximum dose, mean dose, and dose received by 30% volume of individual SGDs, respectively. For better perception of the impact of BT on individual SGDs, the doses received are extrapolated to radical BT dose of 60Gy. RESULTS: For lateralized implants, the highest dose received by ipsilateral parotid (PTD) was 12.3% seen in tonsillar implants. The contralateral PTD receives minimal doses. As expected, the ipsilateral submandibular gland (SMG) received high doses in the range of 80% of the total prescribed dose, whereas contralateral SMG received 10% of ipsilateral dose. For the midline implants, the mean dose range for PTD was 7-11% of the total prescribed dose and for SMG between 17% and 56%, depending on the location. CONCLUSIONS: The study quantifies the percentage doses received by the individual SGDs in interstitial head and neck BT for use in future planning of the BT procedures and for salivary functional studies, prediction of damage, and quality-of-life parameters.

Inter and intraobserver variation in gross tumor delineation on megavoltage CT images in patients undergoing tomotherapy-based image-guided radiotherapy for postoperative vault recurrences.

PURPOSE: This study was designed to evaluate inter and intraobserver concordance in gross tumor volume (GTV) delineation on megavoltage CT (MVCT) images in patients with postoperative vault recurrences. MATERIALS AND METHODS: Three observers delineated GTV on MVCT and CECT and two observers recontoured on MVCT images. Tumor volumes were calculated and correlated using Spearman correlation. The standard deviation of centre of mass was averaged on per patient basis. The ratio of common volume and encompassing volume was used to determine intra and interobserver spatial concordance. Lack of difference in spatial concordance ratio between MVCT and CECT images was used as an index of usability of MVCT images. RESULTS: Thirty six datasets were available for seven patients. High intraobserver GTV correlation was recorded for observer 1 and 2 (r = 0.93 and r = 0.98; P=0.03 and 0.0001). The average intraobserver spatial concordance ratio was 0.57 and 0.62 respectively. The mean GTV of observers 1, 2 and 3 were 31.6 (18.7-52.2); 28.2 (16.7-51.8) and 46.3 cc (29.1-90.5) respectively. Average standard deviation of centre of mass of all observers was less than 5 mm in either direction. Largest interobserver discordance was observed in anterior, inferior and lateral direction. The interobserver spatial concordance of GTV on MVCT and CECT images was 0.34 and 0.36 (P=0.24) respectively. CONCLUSION: Moderate to good inter and intraobserver GTV correlation was observed on MVCT images, however, was associated with low interobserver spatial concordance on both MVCT and CECT images. Strategies to improve contouring reproducibility on MVCT and KVCT images are desirable.

Desmoplastic small round cell tumor of the pancreas: An unusual primary site for an uncommon tumor.

Pancreas is a rare location for desmoplastic small round cell tumor. The present case highlights the dilemma in diagnosis and ascertaining the site of tumor origin. Morphologic and immunohistochemical features were complemented with the molecular markers and tumor origin which was initially nebulous was subsequently confirmed on exploratory laparotomy.

Prognostic factors and outcome in Askin-Rosai tumor: a review of 104 patients.

PURPOSE: To evaluate the prognostic factors and treatment outcome of patients with Askin-Rosai tumor of the chest wall treated at a single institution. METHODS AND MATERIALS: Treatment comprised multiagent chemotherapy and local therapy, which was either in the form of surgery alone, radical external-beam radiotherapy (EBRT) alone, or a combination of surgery and EBRT. Thirty-two patients (40%) were treated with all three modalities, 21 (27%) received chemotherapy and radical EBRT, and 19 (24%) underwent chemotherapy followed by surgery only. RESULTS: One hundred four consecutive patients aged 3-60 years were treated at the Tata Memorial Hospital from January 1995 to October 2003. Most (70%) were male (male/female ratio, 2.3:1). Asymptomatic swelling (43%) was the most common presenting symptom, and 25% of patients presented with distant metastasis. After a median follow-up of 28 months, local control, disease-free survival, and overall survival rates were 67%, 36%, and 45%, respectively. Median time to relapse was 25 months, and the median survival was 76 months. Multivariate analysis revealed age ≥18 years, poor response to induction chemotherapy, and presence of pleural effusion as indicators of inferior survival. Fifty-six percent of patients with metastatic disease at presentation died within 1 month of diagnosis, with 6-month and 5-year actuarial survival of 14% and 4%, respectively. CONCLUSION: Primary tumor size, pleural effusion, response to chemotherapy, and optimal radiotherapy were important prognostic factors influencing outcome. The combination of neoadjuvant chemotherapy, surgery, and radiotherapy resulted in optimal outcome.

Bilateral renal metastases in a case of Merkel cell carcinoma.

Merkel cell carcinoma is a primary neuroendocrine carcinoma of the skin. It is a highly aggressive tumor which commonly metastasizes to lymph nodes, liver, lung and bone. The diagnosis is based on histology and immunohistochemistry. Renal metastasis, with sparing of other common sites of hematogenous spread (lung and liver), is a unique feature of this case.

Evaluation of pediatric abdominal masses by fine-needle aspiration cytology: a clinicoradiologic approach.

The pathologist forms a very important part of the clinical team in the management of pediatric intra-abdominal masses in giving a rapid, accurate diagnosis for these potentially curable tumors. Fine-needle aspiration cytology (FNAC) is an invaluable tool in this regard when interpreted with clinicoradiologic parameters. With this in mind, we decided to evaluate the role of FNAC in pediatric abdominal masses in our institution. A total of 83 of 105 FNAC accessioned in the pathology department over 5 years (2003-2007) were studied. These included only cases where a diagnosis could be offered on cytology. Detailed clinicoradiological features were obtained from hospital records. Cytomorphological features examined included cellularity, architectural pattern, background, key cellular details. Immunocytochemistry were done where necessary. Lesions diagnosed on FNAC included Wilms' tumor (19), lymphoma (10), neuroblastoma (6), hepatoblastoma (5), PNET (5), rhabdomyosarcoma (2), DSRCT (2), germ cell tumor (6), and miscellaneous tumors (7). Definite diagnosis could be offered on cytomorphology in 74.7% (62) cases, while in 25.3% (21) cases only a diagnosis of round cell tumor could be offered. Concordance with final histopathology and biochemical parameters was subsequently obtained in 79/83 (95.5%) of cases. A clinically relevant classification is possible on FNAC in pediatric abdominal tumors when interpreted with clinicoradiologic parameters. This obviates the need for a more time-consuming biopsy procedure in critical situations and in stage II nephroblastoma where it is contraindicated.

Primary vaginal Ewing's sarcoma or primitive neuroectodermal tumor in a 17-year-old woman: a case report.

INTRODUCTION: Primary Ewing's sarcoma or primitive neuroectodermal tumor of the genital tract of women is uncommon. Rarer still is its occurrence in the vagina, with only five cases described so far. Out of these, only one case was confirmed using molecular analysis. CASE PRESENTATION: We present an extremely rare case of Ewing's sarcoma or primitive neuroectodermal tumor in a 17-year-old Indian girl. She presented with a vaginal mass that was initially diagnosed as a malignant round cell tumor. Immunohistochemistry showed diffuse positivity for vimentin, membranous positivity for MIC2, and positivity for BCL2 and FLI-1. On the other hand, she was negative for cytokeratin, epithelial membrane antigen, desmin, Myo D-1, myogenin and smooth muscle actin. A diagnosis of primitive neuroectodermal tumor was thus offered. Furthermore, a molecular analysis of our patient using reverse transcription-polymerase chain reaction technique showed positivity for t(11; 22) (q24; q12) (EWSR1-FLI1), thus confirming the diagnosis of a Ewing's sarcoma/primitive neuroectodermal tumor. Our patient was offered chemotherapy on Institutional protocol EFT 2001. CONCLUSION: This is a rare case of primary vaginal Ewing's sarcoma or primitive neuroectodermal tumor, which was confirmed with molecular analysis, in the youngest patient known so far. This study reinforces the value of integrating morphological features with membranous MIC2 positivity, along with application of molecular techniques in objective identification of an Ewing's sarcoma or primitive neuroectodermal tumor at uncommon sites.

Extraconal orbital tumors in children--a spectrum.

Orbital masses in children are uncommon but extremely challenging problems for clinicians and pathologists due to their critical location and availability of limited diagnostic material. We analyzed 47 specimens comprising biopsies, excision specimens, and FNAC of extraconal pediatric orbital masses (excluding retinoblastoma) accessioned in the pathology department over 5 years in a tertiary referral cancer center. Immunohistochemistry (IHC-74%) and molecular methods (one case) were done where necessary. The chief presenting symptom was proptosis in 55.3% patients and radiologically 53.8% malignant tumors showed extraorbital extension. A diagnostic algorithm was formulated to assess which cases needed pathology evaluation. Malignant round cell tumors (76.6%), chiefly embryonal rhabdomyosarcoma (51%), benign spindle cell neoplasms, and infectious lesions (tuberculosis, fungal infections), were seen. Of the malignant tumors, those confined to the orbit achieved good treatment response and had an event-free follow-up while those with extraorbital spread had poor outcome. Pediatric orbital masses range from completely treatable infectious lesions, surgically resectable benign neoplasms to aggressive malignancies requiring chemotherapy and radiotherapy. Pathologists play a key role in distinguishing these on small biopsy material and expediating accurate treatment thus saving the vision or life of a patient.

Large adrenal ganglioneuroma with left inferior vena cava: implications for surgery.

The contemporaneous occurrence of adrenal ganglioneuroma and left-sided inferior vena cava is uncommon and is previously never reported. We present a case wherein the two entities were fortuitously associated on preoperative imaging. This information facilitated successful surgical resection and avoided catastrophic vascular injury. A review of literature of the common venous anomaly affecting therapeutic decision-making is also presented.

Unicystic ameloblastoma of the mandible masquerading as carcinoma of the oral cavity in a 10-year-old girl.

A case of unicystic ameloblastoma of the mandible in a 10-year-old child is described. In addition to the mandibular swelling the patient also had a proliferative lesion over the alveolus that masqueraded as a neoplastic lesion.